Endo Pharm Part 1

Diabetes and Thyroid

negative feedback (reversible unless from glucocorticoids)

Hormonal secretion is regulated by

Beta cells in pancreas release insulin, liver takes up glucose to make glycogen, body cells take up glucose

Describe the homeostatic mechanism for when blood sugar level rise

alpha cells in pancreas releases glucagon, liver breaks down glycogen

Describe the homeostatic mechanism for when blood sugar level drop

hyperglycemia, glucose intolerance, glucosuria, ketonemia

Characteristics of DM

Type 1 DM (T1DM, IDDM, juvenile-onset)

Which type of DM has NO circulating insulin and needs insulin replacement

Type 2 DM (T2DM, NIDDM, adult-onset)

Which type of DM has insulin resistance with relative insulin deficiency (enough to prevent DKA)

glucocorticoid, immunosuppressant, atypical antipsychotics

Which drugs can induce type 3 (non-pancreatic DM)?

Type 4 DM (gestational DM)

Which type of DM is characterized by a glucose intolerance at onset/recognition of pregnancy

osmotic diuresis (leads to polyuria, polydipsia)

Acute consequences of hyperglycemia

nephropathy, neuropathy, retinopathy, neuropathic pain, gastroparesis, skin ulcers, impaired wound healing

Chronic consequences of hyperglycemia on the microvasculature

IHD, stroke, PVD, ischemia to limb (diabetic foot), fungal infections

Chronic consequences of hyperglycemia on the macrovascular (arterial narrowing)

Acts at insulin receptors on liver (no glucogenolysis/lipolysis), activates insulin-dependent glucose transporters (increase cellular uptake)

MOA for insulin

different amino acids at specific sites (changes onset and duration)

What are the differences between the multiple forms of insulin?

Short t1/2 (3-5 min)

Why can’t insulin be given orally?

lispro, aspart, glulisine, inhaled (15-20 min)

What are the rapid forms of insulin

regular insulin

What are the short forms of insulin

NPH

What are the intermediate forms of insulin

determir, glargine

What are the long forms of insulin

short/rapid acting for after meals, long to maintain basal levels

Describe the typical insulin dosing regimen - individualized to patients

cough, decreases PFTs, lung cancer; No copd peeps

ADRs and C/I for inhaled insulin

meal carb content, blood glucose, concurrent activity

When using an infusion pump, doses of insulin are based on

beta blockers

What medication class blunts the symptoms like tachycardia, sweating, blurred vision, warmth, and trembling from hypoglycemic episodes?

too high of a dose, mismatch between Cmax and food intake, exercise, alcohol

What might cause hypoglycemia

test blood then inject insulin, then eat

What steps can be taken to avoid hypoglycemia?

confusion, drowsiness, weakness

Neurological symptoms of hypoglycemia

lipohypertrophy, lipoatrophy

What can occur at or near the injection site?

patient education, rotate site, mix insulin thoroughly, store medications properly

Ways to avoid lipohypertrophy

Use human insulin

Ways to avoid lipoatrophy

Works at beta islet cells to produce more insulin

MOA for secretagogues (sulfonylureas)

upregulate GLUT transporters (increase insulin sensitivity and uptake), decrease gluconeogenesis

MOA for glitazones

decrease gluconeogenesis

MOA for biguanides (metformin)

stimulate insulin production after eating

MOA for incretin and GLP-1 mimetics

blocks the inactivation of GLP-1 in the blood vessels

MOA for DPP-4 inhibitors

Act on the proximal tubule to decrease the amount of glucose reabsorbed

MOA for SGLT-2 inhibitors

DKA (decrease in blood glucose leads to a decrease of insulin use)

What is a major risk of using SGLT-2s (off-label) in type 1 DM?

chlorpropamide, tolazamide, tolbutamide

Tell me some 1st gen sulfonylureas

gliclazide, glimepiride, glipizide, glyburide

Tell me some 2nd gen sulfonylureas

nateglinide, repaglinide

Tell me some meglitinides

acarbose, miglitol

Tell me some alpha glucosidase inhibitors

pioglitazones, rosiglitazone

Tell me some thiazolidinediones

Exenatide, -gliptins (DPP4 inhibitors), -glutides (GLP analogs)

Which medications are incretin based?

-flozins

Tell me some SGLT-2 inhibitors

semaglutide, liraglutide, tirzepide (GLP/GIP)

Which oral hypoglycemic drugs are approved for weight loss?

decrease gastric acid secretion (slows gastric emptying), decreases food intake (GIP in brain),

MOA for tirzepatide (dual GLP-1 and GIP agonist)

NVD, Abd pain, constipation, intestinal blockages, sunken eyes, gaunt cheeks, wrinkles, muscle wasting, sarcopenia

ADRs for the ozempic girlies

hypoglycemia, GI disturbances, photosensitivity

ADRs for meglitinides and sulfonylureas

DDI, disulfram reaction with alcohol, hypoglycemia in elderly (chlorpropamide)

ADRs for 1st gen sulfonylureas

meglitinides have a rapid onset and short duration

How do meglitinides and sulfonylureas compare

weight gain, DDI

ADRs for meglitinides

pancreatitis

ADRs for Exenatide

HA, nausea

ADRs for DPP4 inhibitors

fluid retention, edema, BBW for CHF

ADRs for thiozolidindiones

HF, HTN

C/I for thiozolidindiones

diarrhea (50% of patients), lactic acidosis

ADRs for metformin

slow carb absorption in gut

MOA for alpha glucosidase inhibitors

diarrhea, flatulence

ADRs for alpha glucosidase inhibitors

Use with mealtime insulin to suppress glucagon, decrease carb absorption in gut

MOA for pramlintide (analog for pancreatic amylin)

BBW for hypoglycemia (check sugars, heart rate, etc)

ADRs for pramlintide

hypotension, dehydration, UTI, decreased bone densities

Other than DKA what are some ADRs for SGLT-2 inhibitors

metformin (that’s why it’s 1st line baby)

What oral hypoglycemic has the LOWEST potential to cause hypoglycemia

weight, blood glucose, HbA1c

When managing hyperglycemia what do we need to monitor?

glucagon, dextrose, oral sugar (if patient is conscious)

Treating hypoglycemia

Insulin, fluid, monitor K+ (insulin shoves K+ into the cell)

Treating DKA

thiazides, glucocorticoids, SGLT-2 off label

Meds with risk of DKA

liothyronine (T3), Levothyroxine (T4), liotrix (T4 & T3)

What drugs are used for the replacement therapy for hypothyroidism?

iodine, potassium iodine, methimazole (prodrug: carbimazole), PTU, radioactive iodine, beta blockers (symptom management only)

What drugs are used for the management of hyperthyroidism?

disrupts hormone synthesis (take 1+ month for effect)

MOA for radioactive iodine (131 I)

blocks organification (No T4, T3, DIT), inhibits NA/I symporter

MOA for Lugol’s solution

prevent iodide organification (No T4, T3, DIT)

MOA for thionamides

prevents peripheral conversion of T4 to T3

MOA for PTU

131 I, sub-total thyroidectomy

ablative treatments for hyperthyroidism

pregnancy, child under 12, Graves, pre-ablative therapy

Palliative treatments for hyperthyroidism are used for

Do not modify the action of the T3 and T4 that’s already there

Why do thionamides and PTU have a delayed effect

methimazole (prodrug: carbimazole)

Examples of thionamides (more potent than PTU)

PTU (watch LFTs for severe hepatitis)

Which drug that impairs thyroid hormone synthesis is preferred during the 1st trimester of pregnancy because it is less likely to cross placenta?

altered taste/smell (methimazole), rash, polyarthritis, reversible agranulocytosis (watch CBC and infection risk)

ADRs for PTU and thionamides

block uptake of iodine via the inhibition of Na/I symporter

MOA for anion inhibitors like Perchlorate and Thiocynate

thionamides, propanolol, KI, prednisolone

Treatment plan for thyroid storm

cross placenta, hypersensitivity to large amounts of iodide, reversible iodism (metallic taste, burning mouth, sore teeth)

ADRs for Lugol’s (SSKI)

propanolol, metroprolol, atenolol (NO PINDOLOL or ACEBUTOLOL)

Which beta blockers can be used for hyperthyroidism

tachycardia, HTN, arrhythmias, angina, tremor, anxiety, insomnia, heat intolerance, HA, weight loss

ADRs from too much T3 (AKA the reason liothyronine isn’t first line)

protein antigencity (rejection), variable hormone concentration, instability

Why do we avoid desiccated thyroid hormone?

Amio, corticosteroids, iodinated contrast media, IFN-alpha, tyrosine kinase inhibitors, immune checkpoint inhibitors

What medications can cause hypothyroidism

Amio, IFN-alpha, immunotherapy, lithium

What medications can cause hyperthyroidism

Insulin, pramlintide, sulfonylureas, meglitinides, GLP-1s, DPP-4 inhibitors, SGLT-2 inhibitors, thiazoliniones, metformin

Which drugs have the highest hypoglycemic risk (Highest to lowest)?